Coordination of pancreatic islet rhythmic activity by delayed negative feedback.

Secretion of insulin from the pancreas is pulsatile, driven by intrinsic oscillations within individual islets of Langerhans. The secretions are coordinated among the many islets distributed throughout the pancreas producing a synchronized rhythm in vivo that is essential for maintaining normal glucose levels. One hypothesized mechanism for the coordination of islet activity is negative feedback, whereby sequestration of glucose in response to elevated insulin leads to a reduction in the blood glucose level that is sensed by the islet population. This global signal of glucose then coordinates the individual islets. In this study, we tested how this coordination mechanism is affected by time delays in the negative feedback, using a microfluidic system to monitor Ca2+ levels in a small population of islets and implementing glucose control through a negative feedback system. We found that islet synchronization occurs even with time delays in the feedback of up to 7 min. We also found that a second, slower closed-loop oscillation period is produced during delayed feedback in which islet oscillations are clustered into episodes. The period of this second oscillatory mode increases with the time delay and appears to be a second stable behavior that coexists with the faster synchronized oscillation. The general conclusion is that islet coordination through negative feedback is a viable means of islet coordination that is robust to delays in the timing of the feedback, and could complement other potential coordination mechanisms such as entrainment by pancreatic ganglia.NEW & NOTEWORTHY Insulin secretion from islets of Langerhans is rhythmic, and these rhythms are coordinated to produce oscillatory plasma insulin levels. Using a combination of microfluidics and computational modeling, we demonstrate that coordination can occur through negative feedback of the type provided by the liver, even if that feedback is delayed by several minutes. We also demonstrate that a second, slower, mode of oscillations can occur when feedback is delayed where faster oscillations are grouped into episodes.

Pulsatile Basal Insulin Secretion Is Driven by Glycolytic Oscillations.

In fasted and fed states, blood insulin levels are oscillatory. While this phenomenon is well studied at high glucose levels, comparatively little is known about its origin under basal conditions. We propose a possible mechanism for basal insulin oscillations based on oscillations in glycolysis, demonstrated using an established mathematical model. At high glucose, this is superseded by a calcium-dependent mechanism.

Functional Diversity of Evolutionary Novelties: Insights from Waterfall-Climbing Kinematics and Performance of Juvenile Gobiid Fishes.

The evolution of novel functional traits can contribute substantially to the diversification of lineages. Older functional traits might show greater variation than more recently evolved novelties, due to the accrual of evolutionary changes through time. However, functional complexity and many-to-one mapping of structure to function could complicate such expectations. In this context, we compared kinematics and performance across juveniles from multiple species for two styles of waterfall-climbing that are novel to gobiid fishes: ancestral "powerburst" climbing, and more recently evolved "inching", which has been confirmed only among species of a single genus that is nested within the clade of powerburst climbers. Similar net climbing speeds across inching species seem, at first, to indicate that this more recently evolved mode of climbing exhibits less functional diversity. However, these similar net speeds arise through different pathways: Sicyopterus stimpsoni from Hawai'i move more slowly than S. lagocephalus from La Réunion, but may also spend more time moving. The production of similar performance between multiple functional pathways reflects a situation that resembles the phenomenon of many-to-one mapping of structure to function. Such similarity has the potential to mask appropriate interpretations of relative functional diversity between lineages, unless the mechanisms underlying performance are explored. More specifically, similarity in net performance between "powerburst" and "inching" styles indicates that selection on climbing performance was likely a limited factor in promoting the evolution of inching as a new mode of climbing. In this context, other processes (e.g., exaptation) might be implicated in the origin of this functional novelty.

FRENCH: Diversité fonctionnelle des innovations évolutives: l'exemple de la cinématique et des performances de grimpe des chutes d'eau des juvéniles de gobies Résumé L'évolution de nouveaux traits fonctionnels peut contribuer significativement à la diversification des lignées. Les traits fonctionnels les plus anciens peuvent montrer plus de variabilité que les plus récents du fait de l'accumulation de changements évolutif au cours du temps. Cependant, ces prédictions peuvent être complexifiées par la diversité des fonctions et par l'implication de plusieurs structures dans une même fonction. Dans ce contexte, nous avons étudié la cinématique et les performances de grimpe des chutes d'eau de plusieurs espèces de gobies utilisant deux styles de grimpe originaux au sein de cette famille: le mode « powerburst ¼ plus ancestral et le mode « inching ¼ qui a évolué plus récemment. Le mode inching n'a été confirmé que pour deux espèces du même genre incluses au sein du clade des powerburst. Des vitesses de grimpe similaires entre les espèces utilisant le mode inching paraissent indiquer que ce mode de grimpe, qui a évolué plus récemment, présente une diversité fonctionnelle moins élevée. Toutefois, la similarité des vitesses de grimpe entre les deux espèces s'explique par des processus différents: le Sicyopterus stimpsoni d'Haiwaï se déplace plus lentement que le S. lagocephalus de La Réunion mais passe plus de temps en mouvement. La production de performances similaires, résultant de processus différents, reflète un phénomène semblable à celui de l'implication de plusieurs structures dans une même fonction. Si les mécanismes sous-jacents ne sont pas explorés, ces similarités peuvent perturber l'interprétation des différences relatives de diversité fonctionnelle entre les lignées. Par ailleurs, les performances de grimpe similaires entre certaines espèces utilisant le mode inching et d'autres le mode powerburst paraissent indiquer que la force de sélection sur les performances de grimpe est sans doute un facteur réduisant l'avantage évolutif du mode de grimpe inching. Dans ce contexte, d'autres mécanismes (e.g., exaptation) pourraient être à l'origine de cette innovation fonctionnelle. Translated to French by Raphael Lagarde (raph.lagarde@gmail.com).

PORTUGESE: Diversidade funcional de novidades evolucionárias: percepções da cinemática da escalada em cascatas e desempenho de peixes juvenis gobiídeos ResumoA evolução de novos traços funcionais pode contribuir substancialmente para a diversificação de linhagens. Os traços funcionais mais antigos podem mostrar maior variação do que as novidades desenvolvidas mais recentemente, devido ao acúmulo de mudanças evolutivas ao longo do tempo. No entanto, a complexidade funcional e os inúmeros mapeamentos de uma estrutura para uma única função podem complicar essas expectativas. Nesse contexto, comparamos a cinemática e a performance em juvenis de várias espécies para dois estilos de escalada em cascata que são novidades em peixes gobiídeos: a ancestral escalada por "explosão" e o evolutivamente mais recente chamado de "avançamento", que foi confirmado apenas entre espécies de um único gênero que dentro do clado de escaladores por explosão. Velocidades finais de escalada semelhantes entre espécies usando "avançamento" parecem, inicialmente, indicar que esse modo de escalada evolutivamente mais recente exibe menor diversidade funcional. No entanto, essas velocidades finais similares ocorrem por diferentes formas: Sicyopterus stimpsoni do Havaí se move mais devagar que S. lagocephalus das Ilhas Reunião, mas pode gastar mais tempo se movendo. Desempenhos semelhantes entre várias vias funcionais refletem uma situação que se assemelha ao fenômeno de mapeamento de uma estrutura para um única função. Essa semelhança tem o potencial de ocultar interpretações apropriadas sobre relativa diversidade funcional entre linhagens, a menos que os mecanismos que afetam o desempenho sejam explorados. Mais especificamente, a semelhança no desempenho final entre os estilos "explosão" e "avançamento"indica que a seleção na performance em escalada provavelmente foi um fator limitante na promoção da evolução por "avançamento" como um novo modo de escalada. Nesse contexto, outros processos (e.g., exaptação) podem estar relacionados com a origem dessa novidade funcional. Translated to Portuguese by Diego Vaz (dbistonvaz@vims.edu).

Melt growth and properties of bulk BaSnO3 single crystals.

We present the first-time growth of bulk BaSnO3 single crystals from the melt by direct solidification, their basic electrical and optical properties as well as their structural quality. Our measurement of the melting point (MP) of BaSnO3 amounts to 1855 °C ± 25 K. At this temperature an intensive decomposition and non-stoichiometric evaporation takes place as the partial pressure of SnO(g) is about 90 times higher than that of BaO(g). X ray powder diffraction identified only the BaSnO3 perovskite phase, while narrow rocking curves having a full width at half maximum of 26 arcsec and etch pit densities below 106 cm-2 confirm a high degree of structural perfection of the single crystals. In this respect they surpass the structural properties of those single crystals that were reported in the literature. The electrical conductivity of nominally undoped crystals depends on the growth conditions and ranges from insulating to medium n-type conductivity. After post-growth annealing in an oxidizing atmosphere undoped crystals are generally insulating. Doping the crystals with lanthanum during growth results in a high n-type conductivity. For a La doping concentration of 0.123 wt.% we measured an electron concentration of 3.3 × 1019 cm-3 and an electron mobility of 219 cm2 V-1 s-1. Based on optical absorption measurements we determined an energy of 3.17 ± 0.04 eV at 5 K and of 2.99 ± 0.04 eV at 297 K for the indirect band gap of BaSnO3.

Nanoscopic yttrium oxide fluorides: non-aqueous fluorolytic sol-gel synthesis and structural insights by 19F and 89Y MAS NMR.

Nanoscopic yttrium acetate fluorides Y(CH(3)COO)(3-z)F(z) and yttrium oxide fluorides YO(3-z)/(2)F(z )were prepared with tunable Y/F molar ratios via the fluorolytic sol-gel route. All samples were characterized by X-ray diffraction, elemental analysis and thermal analysis. In addition, local structures of all samples were studied by (19)F MAS, (19)F-(89)Y CP MAS and (1)H-(89)Y CP MAS NMR spectroscopy and the respective chemical shifts are given. For both classes of compounds, only the fluorination using one equivalent of F (z = 1) leads to defined, well crystalline matrices: yttrium acetate fluoride Y(CH(3)COO)(2)F and r-YOF.

Establishment of a Cre recombinase based mutagenesis protocol for markerless gene deletion in Streptococcus suis.

The lack of knowledge about pathogenicity mechanisms of Streptococcus (S.) suis is, at least partially, attributed to limited methods for its genetic manipulation. Here, we established a Cre-lox based recombination system for markerless gene deletions in S. suis serotype 2 with high selective pressure and without undesired side effects.

Two neural streams, one voice: pathways for theme and variation in the songbird brain.

Birdsong offers a unique model system to understand how a developing brain - once given a set of purely acoustic targets - teaches itself the vocal-tract gestures necessary to imitate those sounds. Like human infants, to juvenile male zebra finches (Taeniopygia guttata) falls the burden of initiating the vocal-motor learning of adult sounds. In both species, adult caregivers provide only a set of sounds to be imitated, with little or no information about the vocal-tract gestures used to produce the sounds. Here, we focus on the central control of birdsong and review the recent discovery that zebra finch song is under dual premotor control. Distinct forebrain pathways for structured (theme) and unstructured (variation) singing not only raise new questions about mechanisms of sensory-motor integration, but also provide a fascinating new research opportunity. A cortical locus for a motor memory of the learned song is now firmly established, meaning that anatomical, physiological, and computational approaches are poised to reveal the neural mechanisms used by the brain to compose the songs of birds.

Olfactory bulb monoamine concentrations vary with time of day.

The olfactory bulb (OB) has been recently identified as a circadian oscillator capable of operating independently of the master circadian pacemaker, the suprachiasmatic nuclei of the hypothalamus. OB oscillations manifest as rhythms in clock genes, electrical activity, and odor sensitivity. Dopamine, norepinephrine, and serotonin have been shown to modulate olfactory information processing by the OB and may be part of the mechanism that underlies diurnal changes in olfactory sensitivity. Rhythmic release of these neurotransmitters could generate OB rhythms in electrical activity and olfactory sensitivity. We hypothesized that these monoamines were rhythmically released in the OB. To test our hypotheses, we examined monoamine levels in the OB, over the course of a day, by high-performance liquid chromatography coupled to electrochemical detection. We observed that dopamine and its metabolite, 3-4-dihydroxyphenylacetic acid, rhythmically fluctuate over the day. In contrast, norepinephrine is arrhythmic. Serotonin and its metabolite hydroxyindoleacetic acid appear to rhythmically fluctuate. Each of these monoamines has been shown to alter OB circuit behavior and influence odor processing. Rhythmic release of serotonin may be a mechanism by which the suprachiasmatic nuclei communicate, indirectly, with the OB.

Two types of burst firing in gonadotrophin-releasing hormone neurones.

Gonadotrophin-releasing hormone (GnRH) neurones fire spontaneous bursts of action potentials, although little is understood about the underlying mechanisms. In the present study, we report evidence for two types of bursting/oscillation driven by different mechanisms. Properties of these different types are clarified using mathematical modelling and a recently developed active-phase/silent-phase correlation technique. The first type of GnRH neurone (1-2%) exhibits slow (∼0.05 Hz) spontaneous oscillations in membrane potential. Action potential bursts are often observed during oscillation depolarisation, although some oscillations were entirely subthreshold. Oscillations persist after blockade of fast sodium channels with tetrodotoxin (TTX) and blocking receptors for ionotropic fast synaptic transmission, indicating that they are intrinsically generated. In the second type of GnRH neurone, bursts were irregular and TTX caused a stable membrane potential. The two types of bursting cells exhibited distinct active-phase/silent-phase correlation patterns, which is suggestive of distinct mechanisms underlying the rhythms. Further studies of type 1 oscillating cells revealed that the oscillation period was not affected by current or voltage steps, although amplitude was sometimes damped. Oestradiol, an important feedback regulator of GnRH neuronal activity, acutely and markedly altered oscillations, specifically depolarising the oscillation nadir and initiating or increasing firing. Blocking calcium-activated potassium channels, which are rapidly reduced by oestradiol, had a similar effect on oscillations. Kisspeptin, a potent activator of GnRH neurones, translated the oscillation to more depolarised potentials, without altering period or amplitude. These data show that there are at least two distinct types of GnRH neurone bursting patterns with different underlying mechanisms.

Prolactin induces a hyperpolarising current in rat paraventricular oxytocinergic neurones.

Prolactin and oxytocin are important reproductive hormones implicated in several common adaptive functions during pregnancy, pseudopregnancy and lactation. Recently, extracellular recordings of supraoptic neurones have shown that prolactin may modulate the electrical activity of oxytocinergic neurones. However, no study has been conducted aiming to establish whether prolactin directly influences this activity in oxytocinergic paraventricular neurones. In the present study, we addressed this question by studying the effects of prolactin on the electrical activity and voltage-current relationship of identified paraventricular neurones in rat brain slices. Whole-cell recordings were obtained and neurones were classified on the basis of their morphological and electrophysiological fingerprint (i.e. magnocellular or parvicellular) and neuropeptide phenotype (i.e. oxytocinergic or non-oxytocinergic). We report that prolactin elicited a hyperpolarising current in 37% of the neurones in this nucleus, of which the majority (67%) were identified as putative magnocellular oxytocin neurones and the reminder (33%) were regarded as oxytocin-negative, parvicellular neuroendocrine neurones. Our results suggest that, in addition to the well-established negative feedback loop between prolactin-secreting lactotrophs and dopaminergic neurones in the arcuate nucleus, an inhibitory feedback loop also exists between lactotrophs and oxytocinergic paraventricular neurones.

Investigating heterogeneity of intracellular calcium dynamics in anterior pituitary lactotrophs using a combined modelling/experimental approach.

Cell responses are commonly heterogeneous, even within a subpopulation. In the present study, we investigate the source of heterogeneity in the Ca(2+) response of anterior pituitary lactotrophs to a Ca(2+) mobilisation agonist, thyrotrophin-releasing hormone. This response is characterised by a sharp increase of cytosolic Ca(2+) concentration as a result of mobilisation of Ca(2+) from intracellular stores, followed by a decrease to an elevated plateau level that results from Ca(2+) influx. We focus on heterogeneity of the evoked Ca(2+) spike under extracellular Ca(2+) free conditions. We introduce a method that uses the information provided by a mathematical model to characterise the source of heterogeneity. This method compares scatter plots of features of the Ca(2+) response obtained experimentally with those made from the mathematical model. The model scatter plots reflect random variation of parameters over different ranges, and matching the experimental and model scatter plots allows us to predict which parameters are most variable. We find that a large degree of variation in Ca(2+) efflux is a likely key contributor to the heterogeneity of Ca(2+) responses to thyrotrophin-releasing hormone in lactotrophs. This technique is applicable to any situation in which the heterogeneous biological response is described by a mathematical model.

A tale of two rhythms: the emerging roles of oxytocin in rhythmic prolactin release.

Hormone secretion often occurs in a pulsatile manner. In this review, we discuss two rhythms of in vivo prolactin release in female rats and the ongoing research that we and others have performed aiming to understand the mechanisms underlying them. The peptide hormone oxytocin appears to play an important role in both rhythms. One rhythm occurs during the first half of pregnancy, but can also be induced in ovariectomised rats. This is characterised by a circadian pattern with two prolactin surges per day. Two methods for triggering this rhythm are discussed, each utilising a unique physiological pathway that includes oxytocin action, presumably on pituitary lactotrophs. The second rhythm occurs during the oestrous cycle and is characterised by a surge of prolactin on the afternoon of pro-oestrus. We discuss recent findings that oxytocin is more effective at stimulating prolactin release from lactotrophs taken from animals on the afternoon of pro-oestrus than from those of animals on the morning of dioestrus 1, raising the possibility that this hormone plays a physiological role in the regulation of prolactin secretion during the oestrous cycle.

Synchronization of pancreatic islet oscillations by intrapancreatic ganglia: a modeling study.

Plasma insulin measurements from mice, rats, dogs, and humans indicate that insulin levels are oscillatory, reflecting pulsatile insulin secretion from individual islets. An unanswered question, however, is how the activity of a population of islets is coordinated to yield coherent oscillations in plasma insulin. Here, using mathematical modeling, we investigate the feasibility of a potential islet synchronization mechanism, cholinergic signaling. This hypothesis is based on well-established experimental evidence demonstrating intrapancreatic parasympathetic (cholinergic) ganglia and recent in vitro evidence that a brief application of a muscarinic agonist can transiently synchronize islets. We demonstrate using mathematical modeling that periodic pulses of acetylcholine released from cholinergic neurons is indeed able to coordinate the activity of a population of simulated islets, even if only a fraction of these are innervated. The role of islet-to-islet heterogeneity is also considered. The results suggest that the existence of cholinergic input to the pancreas may serve as a regulator of endogenous insulin pulsatility in vivo.

Comparison of skeletal muscle strength between cardiac patients and age-matched healthy controls.

The purpose of the present study was to compare muscular strength of knee extensors and arm flexor muscles of cardiac patients (n = 638) and healthy controls (n = 961) in different age groups. Isometric torques were measured in a sitting position with the elbow, hip, and knee flexed to 90(0). For statistical analysis, age groups were pooled in decades from the age of 30 to 90 years. Additionally, the influence of physical lifestyle prior to disease on muscular strength was obtained in the patients. For statistical analysis three-way ANOVA (factors age, gender, and physical activity level) was used.Both in patients and in controls a significant age-dependent decline in maximal torque could be observed for arm flexors and knee extensors. Maximal leg extensor muscle showed statistically significant differences between healthy controls and cardiac patients as well as between subgroups of patients: Physically inactive patients showed lowest torques (male: 148 +/- 18 Nm; female: 82 +/- 25 Nm) while highest values were measured in control subjects (male: 167 +/- 16 Nm; female: 93 +/- 17 Nm). In contrast, arm flexor muscles did not show any significant influence of health status or sports history.This qualitative difference between weight-bearing leg muscles and the muscle group of the upper extremity suggest that lower skeletal muscle strength in heart patients is mainly a consequence of selective disuse of leg muscles rather than any pathological skeletal muscle metabolism. Since a certain level of skeletal muscle strength is a prerequisite to cope with everyday activities, strength training is recommended as an important part of cardiac rehabilitation.

Age-dependent sparing of visual function after bilateral lesions of primary visual cortex.

Bilateral lesions of primary visual cortex (PVC) sustained early in life induce the visual system to undergo structural and functional reorganization and produce modified neuronal networks capable of mediating visual abilities that would be impaired if the lesions occurred in adulthood. Reorganization after early lesion is also accompanied by degeneration of the lateral geniculate nucleus of the thalamus, and 90% of beta retinal ganglion cells die via retrograde degeneration. It is unclear whether the high potential of the system to reorganize after early lesion could overcome the effects of beta retinal ganglion cell death. Visual acuity, which depends on an intact beta-cell array, was impaired in cats that underwent PVC lesions on postnatal day 1 and indicated that neuroplastic potential was insufficient to overcome early lesion-induced maladaptive plasticity. Animals with lesions made at 1 month of age, a stage accompanied by high levels of neuroplastic potential but no death of beta cells, achieved acuity measures equivalent to intact animals. The authors conclude that visual signals are rerouted to subserve functionality when the lesion is made at 1 month of age, but not at 1 day of age.

Continuity conditions and torsion angles from ssNMR orientational restraints.

The backbone torsion angle pair (varphi,psi) at each amino acid of a polypeptide is a descriptor of its conformation. One can use chemical shift and dipolar coupling data from solid-state NMR PISEMA experiments to directly calculate the torsion angles for the membrane-spanning portion of a protein. However, degeneracies inherent in the data give rise to multiple potential torsion angles between two adjacent peptide planes (a diplane). The molecular backbone structure can be determined by gluing together the consecutive diplanes, as in the PIPATH algorithm [T. Asbury, J.R. Quine, S. Achuthan, J. Hu, M.S. Chapman, T.A. Cross, R. Bertram, PIPATH: an optimized alogrithm for generating alpha-helical structures from PISEMA data, J. Magn. Reson. 183 (2006) 87-95.]. The multiplicities in torsion angles translate to multiplicities in diplane orientations. In this paper, we show that adjacent diplanes can be glued together to form a permissible structure only if they satisfy continuity conditions, described quantitatively here. These restrict the number of potential torsion angle pairs. We rewrite the torsion angle formulas from [J.R. Quine, M.T. Brenneman, T.A. Cross, Protein structural analysis from solid-state NMR-drived orientational constraints, Biophys. J. 72 (1997) 2342-2348.] so that they automatically satisfy the continuity conditions. The reformulated torsion angle formulas have been applied recently in the PIPATH algorithm [T. Asbury, J.R. Quine, S. Achuthan, J. Hu, M.S. Chapman, T.A. Cross, R. Bertram, PIPATH: an optimized alogrithm for generating alpha-helical structures from PISEMA data, J. Magn. Reson. 183 (2006) 87-95.] and will be helpful in other applications in which diplane gluing is used to construct a protein backbone model.

Opposite impact on 14C-2-deoxyglucose brain metabolism following patterns of high and low frequency repetitive transcranial magnetic stimulation in the posterior parietal cortex.

Repetitive transcranial magnetic stimulation (rTMS) appears capable of modulating human cortical excitability beyond the duration of the stimulation train. However, the basis and extent of this "off-line" modulation remains unknown. In a group of anesthetized cats, we applied patterns of real or sham focal rTMS to the visuo-parietal cortex (VP) at high (HF) or low (LF) frequency and recorded brain glucose uptake during (on-line), immediately after (off-line), or 1 h after (late) stimulation. During the on-line period LF and HF rTMS induced a significant relative reduction of (14)C-2DG uptake in the stimulated VP cortex and tightly linked cortical and subcortical structures (e.g. the superficial superior colliculus, the pulvinar, and the LPl nucleus) with respect to homologue areas in the unstimulated hemisphere. During the off-line period HF rTMS induced a significant relative increase in (14)C-2DG uptake in the targeted VP cortex, whereas LF rTMS generated the opposite effect, with only mild network impact. Moderate distributed effects were only recorded after LF rTMS in the posterior thalamic structures. No long lasting cortical or subcortical effects were detected during the late period. Our findings demonstrate opposite modulation of rTMS on local and distant effects along a specific network, depending on the pattern of stimulation. Such effects are demonstrated in the anesthetized animal, ruling out behavioral and non-specific reasons for the differential impact of the stimulation. The findings are consistent with previous differential electrophysiological and behavioral effects of low and high frequency rTMS patterns and provide support to uses of rTMS in neuromodulation.

Pattern motion selectivity in population responses of area 18.

It is commonly believed that the complexity of visual stimuli represented by individual neurons increases towards higher cortical areas. However, even in early visual areas an individual neuron's response is influenced by stimuli presented outside its classical receptive field. Thus, it has been proven difficult to characterize the coding of complex stimuli at the level of single neurons. We therefore investigated population responses using optical imaging in cat area 18 to complex stimuli, plaids. Plaid stimuli are composed of two superimposed gratings moving in different directions. They may be perceived as either two separate surfaces or as a global pattern moving in intermediate direction to the components' direction of motion. We found that in addition to activity maps representing the individual components' motion, plaid stimuli produced activity distributions matching the predictions from a pattern-motion model in central area 18. Thereby, relative component- and pattern-like modulations followed the degree of psychophysical pattern bias in the stimulus. Thus, our results strongly indicate that area 18 exhibits a substantial response to pattern-motion signals at the population level suggesting the presence of intrinsic or extrinsic mechanisms that allow for integration of motion responses from far outside the classical receptive field.

PIPATH: an optimized algorithm for generating alpha-helical structures from PISEMA data.

An optimized algorithm for finding structures and assignments of solid-state NMR PISEMA data obtained from alpha-helical membrane proteins is presented. The description of this algorithm, PIPATH, is followed by an analysis of its performance on simulated PISEMA data derived from synthetic and experimental structures. pipath transforms the assignment problem into a path-finding problem for a directed graph, and then uses techniques of graph theory to efficiently find candidate assignments from a very large set of possibilities.